Description of Treatment/Procedure

Obesity is a highly prevalent condition associated with serious comorbid conditions. In treating obesity, the goals are weight loss, reduced morbidity and mortality, and improved quality of life. Weight loss can be achieved by reducing caloric intake (nutritional changes) and/or increasing caloric expenditure (physical activity changes). Drugs may be used to enhance the efficacy of lifestyle changes. This report focuses on orlistat and sibutramine, two drugs approved by the U.S. Food and Drug Administration. Orlistat is a lipase inhibitor that blocks the absorption of ingested fat. Sibutramine is a noradrenaline, serotonin, and, to a lesser extent, dopamine reuptake inhibitor that increases satiety after the onset of eating. Orlistat may produce gastrointestinal side effects that, in most cases, are mild and transient and can be minimized by following a recommended diet. Sibutramine may cause significant increases in blood pressure and pulse rate in a subset of patients and, therefore, monitoring is necessary.

Committee Summary

With regard to pharmacological approaches to weight loss, the ICSI Technology Assessment Committee finds:

1. Sibutramine is safe for most patients. However, due to concerns about hypertension and cardiovascular disease related to sibutramine use, blood pressure and pulse rate should be monitored at regular intervals to identify those patients who experience clinically significant increases in blood pressure or pulse rate during treatment.
   
2. Orlistat is safe for most patients. Gastrointestinal side effects are common but the frequency and severity decrease over time (typically after 1 week) and can be reduced by careful attention to the dietary fat content.
   
3. As an adjunct to intensive nutritional and lifestyle changes, both orlistat and sibutramine are associated with greater weight loss than placebo. With sibutramine, patients can expect a weight loss of 2.4-16.6 kg after 12-52 weeks of treatment. A weight loss of at least 5% of initial body weight at up to 1 year is reported by 27%-88%; a weight loss of at least 10% of initial body weight at up to 1 year is reported by 6%-76%. With orlistat, patients can expect a weight loss of 3.9-10.3 kg after 1 year and 5.0-7.4 kg after 2 years of treatment. A weight loss of at least 5% of initial body weight at 1 year is reported by 33-69%; a weight loss of at least 10% of initial body weight at 1 year is reported by 10-39%. With both drugs, 5%-25% fail to complete the run-in phase of the study; of those who are randomized, 9%-54% of both the active treatment and placebo groups fail to complete the treatment phase of the study. The greatest benefit may be in patients with comorbid conditions such as diabetes. While patients with a comorbid condition may not experience as great a weight loss as patients without the condition, the physiological benefits are important. (Conclusion Grade I)
   
4. Programs in which >50% of patients lose >5% of initial body weight and >30% of patients lose >10% of initial body weight are characterized by a placebo run-in period that identified individuals willing and able to make changes in their nutritional and activity patterns; information on behavior modification, changing nutritional choices, and increasing physical activity; regular monitoring in a clinic setting; and exclusion criteria that exclude patients with serious disease, major depression, and substance abuse.
   
5. To date, the longest reported follow-up is 2 years. There is little published evidence to suggest that orlistat or sibutramine are effective in maintenance of weight loss for longer than 2 years or in decreasing long-term morbidity or mortality. Possible harms associated with long-term use of orlistat or sibutramine are unknown.